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Baraa Noueihed, Martine Blais, Jose Carlos Rivera, Ankush Madaan, Sylvain Chemtob; Bone marrow-derived stem cells repair retinal vasculature in mouse model of oxygen-induced retinopathy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2217.
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© ARVO (1962-2015); The Authors (2016-present)
Retinopathy of prematurity (ROP) is the leading cause of blindness in young children. The genesis of ROP progresses through two phases: 1) upon exposure to high O2 compared to that in utero, a process of retinal vaso-attenuation and vaso-obliteration takes place during arrest of microvascular development. 2) As a result of ensuing tissue ischemia an exaggerated neovascularization penetrates abnormally the vitreous predisposing to tragic retinal detachment. Accordingly, preservation of the microvasculature during the vaso-obliterative phase would be ideal. Because stem cells have been found to enhance coronary and renal revascularization following an ischemic insult, we surmised that stem cells can accelerate normal revascularization of the retina and in turn prevent aberrant intra-vitreal neovascularization.
Oxygen induced retinopathy (OIR) model of ROP replicates both phases of ROP genesis and was used herein. Two different cell types were isolated from mouse bone marrow: lineage negative (Lin-) hematopoietic stem cells and mesenchymal stem cells (MSC). Lin- cells were isolated by depleting the bone marrow mononuclear cells of mature cell types. MSCs were isolated in culture according to their natural adherence quality. These cells were then injected into the vitreous of OIR mice at postnatal day (P) 12 and retinas were analyzed at P17. Similarly, retinas were injected with MSC conditioned media.
Mouse retinas collected at P17 from both MSC and Lin- injected intravitreally localized to the inner retina. Furthermore, mouse retinas injected with MSC or MSC conditioned media showed significant reduction in neovascularization and vaso-obliteration areas in comparison to Lin- injected retinas in OIR. To elucidate potential mechanisms to explain protective effects of MSC, we determined the expression of potentially relevant genes. Analysis revealed a 2-fold increase in the anti-inflammatory cytokine IL-10 and a 2-fold decrease in the pro-inflammatory cytokine IL-1β, along with an increase in pro-angiogenic growth factors VEGFA and FGF.
Findings reveal that bone marrow derived MSC migrate to the retina of OIR mice model and promote proper vascular repair (notably normal revascularization) via paracrine mechanisms involving decrease in pro-inflammatory cytokines and increase in cyto-protective growth factors. MSCs may exert therapeutic benefits in ROP.
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